Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of R/RMM

Inclusion Criteria:

• Patient or his or her legal guardian voluntarily participates in and signs aninformed consent form.

• Aged ≥ 18 years and ≤ 75 years.

• Diagnosed as Multiple Myeloma (MM) according to the international standard formultiple myeloma (IMWG 2014).

• Diagnosed as relapsed/refractory disease or primary refractory disease; relapse isdefined as disease progression within 60 days of the most recent treatment withthree or more lines of therapy with different mechanisms of action; refractory isdefined as failure to achieve MR or above efficacy with prior treatment and diseaseprogression with recent treatment, or disease progression within 60 days oftreatment.

• Flow cytometry or immunohistochemistry showed positive BCMA expression in myelomacells.

• Have not been treated with antibody-based drugs within 2 weeks prior to celltherapy.

• ECOG score 0-2 points.

• HGB≥70g/L，PLT≥30×10^9/L.

• Liver, kidney and cardiopulmonary functions meet the following requirements:

1. Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) >30ml/min；

2. Left ventricular ejection fraction (LVEF) ≥50%,

3. Baseline peripheral oxygen saturation > 90%;

4. Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

Exclusion Criteria:

• Previous diagnosis and treatment of other malignancies within 3 years;

• Presence of one of the following cardiac criteria: atrial fibrillation; Myocardialinfarction within the last 12 months; Prolonged QT syndrome or secondary QTprolongation, as judged by the investigator. Echocardiogram LVSF <30% or LVEF <50%;Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New YorkHeart Association) III or IV (absence of this symptom confirmed by echocardiographywithin 12 months of treatment);

• Patients with active GVHD;

• Patients with a history of severe pulmonary impairment disease;

• Combined with other malignant tumors in the advanced stage;

• Co-infection with severe or persistent infection that cannot be effectivelycontrolled;

• Combined with severe autoimmune disease or congenital immunodeficiency;

• Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA ≥ 500 IU/ml andabnormal liver function] or hepatitis C antibody [HCV-Ab] positive, HCV-RNA abovethe lower limit of detection of the analytical method and abnormal liver function);

• Human immunodeficiency virus (HIV) infection or syphilis infection;

• Patients with a history of severe allergy to biological products (includingantibiotics);

• Patients with central nervous system disorders such as uncontrolled epilepsy,cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;

• Pregnant or Lactating Women; Patients and his or her spouses have a fertility planwithin 12 months after CAR-T cell infusion;

• Other conditions considered inappropriate by the researcher.